Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
July-2020 Volume 20 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
July-2020 Volume 20 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Effects and mechanism of the bile acid (farnesoid X) receptor on the Wnt/β‑catenin signaling pathway in colon cancer

  • Authors:
    • Jiayu Mao
    • Xueqi Chen
    • Chunsaier Wang
    • Wenbin Li
    • Jingnan Li
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing 100730, P.R. China
    Copyright: © Mao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 337-345
    |
    Published online on: April 16, 2020
       https://doi.org/10.3892/ol.2020.11545
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

The downregulation of farnesoid X receptor (FXR; gene name, nuclear receptor subfamily 1 group h member 4), an enteric nuclear bile acid receptor, has been reported in colorectal carcinoma (CRC), and FXR expression has been inversely correlated with CRC stage and clinical outcome. FXR knockdown in chronic colitis mouse models of intestinal tumorigenesis results in early mortality and increased tumor progression via promoting Wnt signaling. The aim of the present study was to explore the effects and mechanism of FXR on the Wnt/β‑catenin signal pathway in CRC. FXR and β‑catenin protein expression levels were detected in an ulcerative colitis mouse model and human colon cancer cell lines (HT‑29, Caco‑2 and HCT‑116). Gain‑ and loss‑of‑function studies were conducted by transfecting colon cancer cells with FXR siRNA and treating them with the FXR agonist GW4064. Subsequently, β‑catenin transcriptional activity was measured using the dual‑luciferase assay, and β‑catenin/TCF4 complex levels and β‑catenin protein and mRNA expression levels were determined. FXR and β‑catenin expression levels were inversely associated in both the animal model and colon cancer cells. The Wnt signaling pathway was activated by increased β‑catenin/TCF4 complex levels upon FXR silencing; however, mRNA and protein levels of β‑catenin were not significantly affected. The FXR agonist GW4064 significantly inhibited the proliferation of cells but promoted the transcriptional activity of β‑catenin. Thus, the present study demonstrated that FXR influences the Wnt/β‑catenin signaling pathway. Furthermore, loss of FXR expression promotes the transcriptional activity of β‑catenin, whereas FXR activation results in the opposite effect.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Reddy BS: Diet and excretion of bile acids. Cancer Res. 41:3766–3768. 1981.PubMed/NCBI

2 

Lagergren J, Ye W and Ekbom A: Intestinal cancer after cholecystectomy: Is bile involved in carcinogenesis? Gastroenterology. 121:542–547. 2001. View Article : Google Scholar : PubMed/NCBI

3 

Peterlik M: Role of bile acid secretion in human colorectal cancer. Wien Med Wochenschr. 158:539–541. 2008. View Article : Google Scholar : PubMed/NCBI

4 

Pearson JR, Gill CI and Rowland IR: Diet, fecal water, and colon cancer-development of a biomarker. Nutr Rev. 67:509–526. 2009. View Article : Google Scholar : PubMed/NCBI

5 

Kundu S, Kumar S and Bajaj A: Cross-talk between bile acids and gastrointestinal tract for progression and development of cancer and its therapeutic implications. IUBMB Life. 67:514–523. 2015. View Article : Google Scholar : PubMed/NCBI

6 

Degirolamo C, Modica S, Palasciano G and Moschetta A: Bile acids and colon cancer: Solving the puzzle with nuclear receptors. Trends Mol Med. 17:564–572. 2011. View Article : Google Scholar : PubMed/NCBI

7 

Modica S, Gofflot F, Murzilli S, D'Orazio A, Salvatore L, Pellegrini F, Nicolucci A, Tognoni G, Copetti M, Valanzano R, et al: The intestinal nuclear receptor signature with epithelial localization patterns and expression modulation in tumors. Gastroenterology. 138:636–648, 648.e1-12. 2010. View Article : Google Scholar : PubMed/NCBI

8 

Bailey AM, Zhan L, Maru D, Shureiqi I, Pickering CR, Kiriakova G, Izzo J, He N, Wei C, Baladandayuthapani V, et al: FXR silencing in human colon cancer by DNA methylation and KRAS signaling. Am J Physiol Gastrointest Liver Physiol. 306:G48–G58. 2014. View Article : Google Scholar : PubMed/NCBI

9 

Lax S, Schauer G, Prein K, Kapitan M, Silbert D, Berghold A, Berger A and Trauner M: Expression of the nuclear bile acid receptor/farnesoid X receptor is reduced in human colon carcinoma compared to nonneoplastic mucosa independent from site and may be associated with adverse prognosis. Int J Cancer. 130:2232–2239. 2012. View Article : Google Scholar : PubMed/NCBI

10 

Frankenberg T, Rao A, Chen F, Haywood J, Shneider BL and Dawson PA: Regulation of the mouse organic solute transporter alpha-beta, Ostalpha-Ostbeta, by bile acids. Am J Physiol Gastrointest Liver Physiol. 290:G912–G922. 2006. View Article : Google Scholar : PubMed/NCBI

11 

De Gottardi A, Touri F, Maurer CA, Perez A, Maurhofer O, Ventre G, Bentzen CL, Niesor EJ and Dufour JF: The bile acid nuclear receptor FXR and the bile acid binding protein IBABP are differently expressed in colon cancer. Dig Dis Sci. 49:982–989. 2004. View Article : Google Scholar : PubMed/NCBI

12 

Gadaleta RM, van Erpecum KJ, Oldenburg B, Willemsen EC, Renooij W, Murzilli S, Klomp LW, Siersema PD, Schipper ME, Danese S, et al: Farnesoid X receptor activation inhibits inflammation and preserves the intestinal barrier in inflammatory bowel disease. Gut. 60:463–472. 2011. View Article : Google Scholar : PubMed/NCBI

13 

Modica S, Murzilli S, Salvatore L, Schmidt DR and Moschetta A: Nuclear bile acid receptor FXR protects against intestinal tumorigenesis. Cancer Res. 68:9589–9594. 2008. View Article : Google Scholar : PubMed/NCBI

14 

Gadaleta RM, Garcia-Irigoyen O and Moschetta A: Bile acids and colon cancer: Is FXR the solution of the conundrum? Mol Aspects Med. 56:66–74. 2017. View Article : Google Scholar : PubMed/NCBI

15 

Korinek V, Barker N, Morin PJ, van Wichen D, de Weger R, Kinzler KW, Vogelstein B and Clevers H: Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/-colon carcinoma. Science. 275:1784–1787. 1997. View Article : Google Scholar : PubMed/NCBI

16 

Mizushima T, Nakagawa H, Kamberov YG, Wilder EL, Klein PS and Rustgi AK: Wnt-1 but not epidermal growth factor induces beta-catenin/T-cell factor-dependent transcription in esophageal cancer cells. Cancer Res. 62:277–282. 2002.PubMed/NCBI

17 

Ni D, Liu J, Hu Y, Liu Y, Gu Y, Zhou Q and Xie Y: A1CF-Axin2 signal axis regulates apoptosis and migration in Wilms tumor-derived cells through Wnt/β-catenin pathway. Vitro Cell Dev Biol Anim. 55:252–259. 2019. View Article : Google Scholar

18 

Xin Y, He L, Luan Z, Lv H, Yang H, Zhou Y, Zhao X, Zhou W, Yu S, Tan B, et al: E-cadherin mediates the preventive effect of Vitamin D3 in Colitis-associated Carcinogenesis. Inflamm Bowel Dis. 23:1535–1543. 2017. View Article : Google Scholar : PubMed/NCBI

19 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

20 

Liu X, Zhang X, Ji L, Gu J, Zhou M and Chen S: Farnesoid X receptor associates with β-catenin and inhibits its activity in hepatocellular carcinoma. Oncotarget. 6:4226–4238. 2015.PubMed/NCBI

21 

Peng Z, Raufman JP and Xie G: Src-mediated cross-talk between farnesoid X and epidermal growth factor receptors inhibits human intestinal cell proliferation and tumorigenesis. PLoS One. 7:e484612012. View Article : Google Scholar : PubMed/NCBI

22 

Tanaka T, Kohno H, Suzuki R, Yamada Y, Sugie S and Mori H: A novel inflammation-related mouse colon carcinogenesis model induced by azoxymethane and dextran sodium sulfate. Cancer Sci. 94:965–973. 2003. View Article : Google Scholar : PubMed/NCBI

23 

Cavard C, Colnot S, Audard V, Benhamouche S, Finzi L, Torre C, Grimber G, Godard C, Terris B and Perret C: Wnt/beta-catenin pathway in hepatocellular carcinoma pathogenesis and liver physiology. Future Oncol. 4:647–660. 2008. View Article : Google Scholar : PubMed/NCBI

24 

Cancer Genome Atlas Network, . Comprehensive molecular characterization of human colon and rectal cancer. Nature. 487:330–337. 2012. View Article : Google Scholar : PubMed/NCBI

25 

Fu T, Coulter S, Yoshihara E, Oh TG, Fang S, Cayabyab F, Zhu Q, Zhang T, Leblanc M, Liu S, et al: FXR regulates intestinal cancer stem cell proliferation. Cell. 176:1098–1112.e18. 2019. View Article : Google Scholar : PubMed/NCBI

26 

Thompson MD, Moghe A, Cornuet P, Marino R, Tian J, Wang P, Ma X, Abrams M, Locker J, Monga SP and Nejak-Bowen K: β-Catenin regulation of farnesoid X receptor signaling and bile acid metabolism during murine cholestasis. Hepatology. 67:955–971. 2018. View Article : Google Scholar : PubMed/NCBI

27 

Zhang R, Nakao T, Luo J, Xue Y, Cornuet P, Oertel M, Kosar K, Singh S and Nejak-Bowen K: Activation of WNT/Beta-catenin signaling and regulation of the Farnesoid X Receptor/Beta-catenin complex after murine bile duct ligation. Hepatol Communications. 3:1642–1655. 2019. View Article : Google Scholar

28 

Maran RR, Thomas A, Roth M, Sheng Z, Esterly N, Pinson D, Gao X, Zhang Y, Ganapathy V, Gonzalez FJ and Guo GL: Farnesoid X receptor deficiency in mice leads to increased intestinal epithelial cell proliferation and tumor development. J Pharmacol Exp Ther. 328:469–477. 2009. View Article : Google Scholar : PubMed/NCBI

29 

Sawa M, Masuda M and Yamada T: Targeting the Wnt signaling pathway in colorectal cancer. Expert Opin Ther Targets. 20:419–429. 2016. View Article : Google Scholar : PubMed/NCBI

30 

Mulholland DJ, Dedhar S, Coetzee GA and Nelson CC: Interaction of nuclear receptors with the Wnt/β-catenin/Tcf signaling axis: Wnt you like to know? Endocr Rev. 26:898–915. 2006. View Article : Google Scholar

31 

Xiao JH, Ghosn C, Hinchman C, Forbes C, Wang J, Snider N, Cordrey A, Zhao Y and Chandraratna RA: Adenomatous polyposis coli (APC)-independent regulation of beta-catenin degradation via a retinoid X receptor-mediated pathway. J Biol Chem. 278:29954–29962. 2003. View Article : Google Scholar : PubMed/NCBI

32 

Han A, Tong C, Hu D, Bi X and Yang W: A direct protein-protein interaction is involved in the suppression of beta-catenin transcription by retinoid X receptor alpha in colorectal cancer cells. Cancer Biol Ther. 7:454–459. 2008. View Article : Google Scholar : PubMed/NCBI

33 

Palmer HG, González-Sancho JM, Espada J, Berciano MT, Puig I, Baulida J, Quintanilla M, Cano A, de Herreros AG, Lafarga M and Muñoz A: Vitamin D(3) promotes the differentiation of colon carcinoma cells by the induction of E-cadherin and the inhibition of beta-catenin signaling. J Cell Biol. 154:369–387. 2001. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Mao J, Chen X, Wang C, Li W and Li J: Effects and mechanism of the bile acid (farnesoid X) receptor on the Wnt/β‑catenin signaling pathway in colon cancer. Oncol Lett 20: 337-345, 2020.
APA
Mao, J., Chen, X., Wang, C., Li, W., & Li, J. (2020). Effects and mechanism of the bile acid (farnesoid X) receptor on the Wnt/β‑catenin signaling pathway in colon cancer. Oncology Letters, 20, 337-345. https://doi.org/10.3892/ol.2020.11545
MLA
Mao, J., Chen, X., Wang, C., Li, W., Li, J."Effects and mechanism of the bile acid (farnesoid X) receptor on the Wnt/β‑catenin signaling pathway in colon cancer". Oncology Letters 20.1 (2020): 337-345.
Chicago
Mao, J., Chen, X., Wang, C., Li, W., Li, J."Effects and mechanism of the bile acid (farnesoid X) receptor on the Wnt/β‑catenin signaling pathway in colon cancer". Oncology Letters 20, no. 1 (2020): 337-345. https://doi.org/10.3892/ol.2020.11545
Copy and paste a formatted citation
x
Spandidos Publications style
Mao J, Chen X, Wang C, Li W and Li J: Effects and mechanism of the bile acid (farnesoid X) receptor on the Wnt/β‑catenin signaling pathway in colon cancer. Oncol Lett 20: 337-345, 2020.
APA
Mao, J., Chen, X., Wang, C., Li, W., & Li, J. (2020). Effects and mechanism of the bile acid (farnesoid X) receptor on the Wnt/β‑catenin signaling pathway in colon cancer. Oncology Letters, 20, 337-345. https://doi.org/10.3892/ol.2020.11545
MLA
Mao, J., Chen, X., Wang, C., Li, W., Li, J."Effects and mechanism of the bile acid (farnesoid X) receptor on the Wnt/β‑catenin signaling pathway in colon cancer". Oncology Letters 20.1 (2020): 337-345.
Chicago
Mao, J., Chen, X., Wang, C., Li, W., Li, J."Effects and mechanism of the bile acid (farnesoid X) receptor on the Wnt/β‑catenin signaling pathway in colon cancer". Oncology Letters 20, no. 1 (2020): 337-345. https://doi.org/10.3892/ol.2020.11545
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team